A mixture of murine leukemia viruses (MuLV) , termed LP-BM5 MuLV, induces a syndrome characterized by lymphoproliferation and immunodeficiency (MAIDS) in susceptible strains of mice. The components of this virus mixture have been characterized by combined biologic and molecular cloning techniques. Biologically cloned ecotropic MuLV and a series of MCF MuLV did not induce MAIDS alone or in combination, suggesting the activity of another virus component. Molecular genetic analyses of the virus mixture revealed the presence of an additional 4.9 kb defective genome that was regularly associated with the development of disease. The ecotropic and 4.9 kb molecular species were molecularly cloned and shown, in combination, to induce changes characteristic of MAIDS. Sequence analyses of the 4.9 kb genome demonstrated that it was most likely derived by an initial recombination between the ecotropic virus and endogenous MCF-like sequences followed by deletion and mutation. The most highly conserved region of the 4.9 kb virus in relation to the ecotropic parent is in gag with the aminoterminal portion of p12 being the most divergent. Further studies will be directed at determining the molecular features of the defective genome responsible for MAIDS induction.